1. Field of the Invention (Technical Field)
This invention relates to health supplement compositions, specifically those utilizing antioxidants or phosphatides, and their use.
2. Background Art
Note that the following discussion refers to a number of publications by author(s) and year of publication, and that due to recent publication dates certain publications are not to be considered as prior art vis-a-vis the present invention. Discussion of such publications herein is given for more complete background and is not to be construed as an admission that such publications are prior art for patentability determination purposes.
Health supplements are used by millions of Americans everyday, ranging from single ingredient vitamin supplements to multi-vitamins to prescription supplements incorporating hormone therapy and other medicinal treatments. A broad number of these health supplements are readily available to the public in over-the-counter formulations, many touting condition specific uses, such as the recent spate of xe2x80x9cultimate anti-aging formulations.xe2x80x9d One of these formulations contains 65 components and suggests ingestion of over 10,000 mg of the combination per day which, due to limitations of tablet size, requires ingesting ten tablets each day. More popular brands of multivitamins contain between 26 ingredients (Theragran-Mxe2x80x94by Mead Johnson) and 53 ingredients (Maxilife Phytoxe2x80x94by Twinlab). These xe2x80x9cshotgunxe2x80x9d approaches of incorporating all possible useful ingredients face not only serious criticisms, but also present serious potential dangers to a user. (See, Sardi, B. xe2x80x9cWhat""s Best in a Multivitamin,xe2x80x9d 2d Ed. (1998), San Dimas, Calif., Sardi Publications, pp. 67-77.) For example, riboflavin (vitamin B2) is known to be toxic in doses above 10 mg per day. Many supplement formulations exceed this limit, posing a potential health risk to the users.
Many health supplement formulations include substantial numbers of herbal compounds. Herbal compounds naturally contain numerous active chemical groups. These active chemical groups compete for overall effect. For example, lemon fruit has an acid content, but counterintuitively, has an alkaline effect within the human body. Grapefruit contains antioxidant herbal substances which can interfere with drugs such as felodipine (Plendil(copyright)) or nifedipine (Procardia(copyright)). It is intuitive that indiscriminate combinations of numerous herbs, each containing numerous key constituents, might have a subtractive overall effect. Garlic is often used in formulations for its antioxidant properties, but may have the side effect of combining with other components in the formulation to exceed safe limits of selenium (200 mcg/day), due to garlic""s relatively high selenium content. Therefore, many supplements on the market incorporating herbal compounds may be more harmful than xe2x80x9chealthful.xe2x80x9d
One promising way to incorporate important supplement components while reducing the potential for high dose toxicity is to utilize synergistic relationships among components. xe2x80x9cPharmacologic synergyxe2x80x9d is a complementary, superadditive response resulting from the combination of two or more agents. For example, there are numerous examples of synergy between antioxidant vitamins. U.S. Pat. No. 5,994,322 to Masuda cites a lecithin-vitamin B12 combination as synergistic. The oxidative synergy of vitamin E and phospholipid have been demonstrated as better than vitamin E alone. (See, Tesories, L., et al., xe2x80x9cSynergistic Interactions Between Vitamin A and Vitamin E Against Lipid Peroxidation in Phosphatidylcholine Liposomes,xe2x80x9d Archives Biochemistry Biophysiology, (1996), vol. 326(1), pp. 57-63.) Vitamin A and vitamin E have more antioxidant synergy with phosphatidylcholine liposomes than the respective single components. Other studies on synergy between numerous compounds for a focused outcome are surprisingly sparse.
On the flip side, other supplement formulations do not provide enough of certain supplements. Although many health supplements contain choline, a member of the B vitamin group, their formulations do not adequately address the needs created by phospholipid physiology. Phosphatidylcholine (either as a phosphomonoester or phosphodiester), is the serum transport form of choline. As can be seen in FIG. 1, phosphatidylcholine (monoester form) has a substitution on either R1 or R2, but not on both. (Choline is depicted for comparison to phosphatidylcholine.) This form of choline is a principle component of all cell membranes. It is especially important to have a sufficient amount of phosphatidylcholine to maintain intact nerve cell membranes. For example, cholinergic nerve cells in particular, when faced with a reduced level of serum phosphatidylcholine, will resort to autocannibalism of the phosphatidylcholine in their cell membranes to maintain their primary mission: producing the neurotransmitter acetylcholine. This degenerates nerve cell membranes, resulting in conditions such as Alzheimer""s Disease related dementia. (See, Summers, W. K. Correspondence: Oral Tetrahydroaminoacridine in the Treatment of Senile Dementia, Alzheimer""s Type, New England Journal of Medicine, vol. 316, p. 1605, (1987).) The choline in phosphatidylcholine is also the principle source of choline metabolized into two other forms of phosphatides: sphingolipids and plasmalogens. Both of these forms are necessary for proper function of the central nervous system.
One of the more important focuses of health supplements is the reduction of free radicals. Free radicals are associated with aging of the brain. (See, Halliwell, B., Gutteridge, J. M. C. xe2x80x9cFree Radicals in Biology and Medicinexe2x80x9d (3rd ed.), (1999) New York, Oxford University Press.) Oxidative injury to the nervous system has been documented in diseases such as AIDS-associated dementia, Alzheimer""s disease, benign senile forgetfulness (pre-Alzheimer""s disorder), Down""s syndrome-associated dementia, Lewy body dementia, multi-infarct dementia, multiple sclerosis, Parkinson""s disease-associated dementia, tardive dyskinesia, Wernicke-Korsakoff syndrome, and alcoholism-associated dementia. Indeed, oxidative injury may be the final common pathway leading to cell death. (See, Joaquin, A. M. et al., xe2x80x9cFunctional Decline in Aging and Disease: A Role for Apoptosis,xe2x80x9d Journal American Geriatrics Society, (2001), vol. 49, pp. 1234-1240.) Numerous studies have shown benefit from the use of antioxidants in many of these disorders. (See, Halliwell, B., Gutteridge, J. M. C., xe2x80x9cFree Radicals in Biology and Medicinexe2x80x9d (3rd ed.), (1999) New York, Oxford University Press.)
Antioxidants are substances that protect against oxidative stress damage caused by free radicals. There are four generally recognized groups of antioxidants: plant extracts, vitamins, amino acids, and minerals. Vitamins are organic substances provided in relatively small quantities from the environment that are necessary for the maintenance of health. Precursors (e.g., carotene for vitamin A), vitamins having multiple forms (e.g., pyridoxine, pyridoxal, pyridoxamine), and essential oligopeptides are typically referred to as xe2x80x9cvitamers,xe2x80x9d hereinafter to be understood as interchangeable with the term xe2x80x9cvitamin.xe2x80x9d
As discussed above, prior art supplement compositions generally take a xe2x80x9cshotgunxe2x80x9d approach of providing supplements instead of providing specific formulations for other than a generalized xe2x80x9canti-agingxe2x80x9d or xe2x80x9cenergyxe2x80x9d formulation. However, U.S. Pat. No. 6,048,846 to Cochran discloses a combination of supplement components designed to fight the causes of disease. The essential combination disclosed is use of at least one hormone with the supplement components. However, hormone administration can be dangerous given the potential downstream effects. This is the result of interaction with other hormones in feedback systems. The dosage range of hormones is often specific to timing of administration within the relevant physiological cycle. The ""846 Patent formulation also does not necessarily result in an antioxidant net effect. For example, iron is used as a preferred mineral. Iron easily forms free radicals. Therefore, iron inclusion can cause a reduction in available antioxidants.
The present invention overcomes the problems associated with a xe2x80x9cshotgunxe2x80x9d supplement approach. The dosage ranges and use of synergistic component relationships overcome problems with potential toxicity. Additionally, as a targeted composition specific to neuroceuticals, the present invention provides appropriate dosages for treatment and reversal of the effects of neurological disorders in addition to addressing the causes. There is a long-felt need in the art for a supplement composition that addresses ongoing neurological degeneration while avoiding toxic dosages of supplements.
Surprisingly, and contrary to the teachings of the prior art, certain combinations of substances are found to give improved nervous system function with improved cognitive function and mental energy. The present invention is a supplement combination including at least one, and preferably at least two, phosphoesters and at least one antioxidant, preferably comprising at least one but not more than five antioxidant amino acids and at least one but not more than fifteen antioxidant vitamins and at least one antioxidant mineral.
The composition of the present invention exhibits synergistic antioxidant and restorative effects on the nervous system effective in treating neurodegenerative disorders where oxidative injury is believed to be contributory. These synergistic effects additionally allow use of lower doses of most of the individual components.
The present invention is a health supplement composition for mammals comprising at least one phosphoester and at least one synergistic antioxidant combination, wherein the synergistic antioxidant combination comprises at least one antioxidant and at least one other composition component that has a synergistic relationship with the antioxidant.
The composition of the present invention comprises at least one application method selected from the group consisting of oral, parenteral, rectal, and topical administration. Further, administration on mammals comprises prevention or treatment of illnesses selected from the group consisting of AIDS-associated dementia, Alzheimer""s disease, benign senile forgetfulness, Down""s syndrome-associated dementia, Lewy body dementia, multi-infarct dementia, multiple sclerosis, Parkinson""s disease-associated dementia, tardive dyskinesia, Wernicke-Korsikoff syndrome, and alcoholism-associated dementia.
The phosphoester of the composition of the present invention is selected from the group consisting of phoshatidylcholine, phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol. Preferably, two phosphoesters are used in the composition.
The antioxidant combination of the present invention comprises at least one member selected from the group of antioxidants consisting of herbal, amino acid, mineral, and vitamin antioxidants. The herbal antioxidant comprises at least one member selected from compounds derived from the group consisting of citrus fruits, citrus peels, curcuma, ginkgo biloba, ginseng, gotu kola, proanthocyanidins, quercetin, and Siberian ginseng. The amino acid antioxidant comprises at least one member selected from the group consisting of acetyl-L-camitine, L-glutamine, N-acetyl-L-cystine, L-lysine, L-methionine, and L-taurine. The antioxidant vitamin comprises at least one member selected from the group consisting of vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B12, beta-carotene, vitamin C, vitamin E, L-glutathione, lipoic acid, lutein, lycopene, ubiquinone, and zeaxanthin. The antioxidant mineral comprises at least one member selected from the group consisting of boron, chromium, manganese, magnesium, selenium, and zinc.
The phosphoester of the composition may comprise a daily dosage of between approximately 0 mg and approximately 16,000 mg of phosphatidylcholine, between approximately 0 mg and approximately 300 mg of phosphatidylserine, between approximately 0 mg and approximately 500 mg of phosphatidylethanolamine, and between approximately 0 mg and approximately 10,000 mg of phosphatidylinositol. The phosphoester of the composition preferably comprises a daily dosage of between approximately 0 mg and approximately 1000 mg of phosphatidylcholine, between approximately 0 mg and approximately 100 mg of phosphatidylserine, between approximately 0 mg and approximately 200 mg of phosphatidylethanolamine, and between approximately 0 mg and approximately 1000 mg of phosphatidylinositol.
The herbal antioxidant of the composition comprises a daily dosage of between approximately 0 mg and approximately 7 mg of barberry, between approximately 0 mg and approximately 70 mg of bilberry proanthocyanidins, between approximately 0 mg and approximately 150 mg of lemon bioflavinoids, between approximately 0 mg and approximately 150 mg of lime bioflavinoids, between approximately 0 mg and approximately 150 mg of orange bioflavinoids, between approximately 0 mg and approximately 1000 mg of curcuma, between approximately 0 mg and approximately 2 mg of garlic bioflavinoids, between approximately 0 mg and approximately 180 mg of ginko biloba, between approximately 0 mg and approximately 2000 mg of ginseng, between approximately 0 mg and approximately 100 mg of gotu kola, between approximately 0 mg and approximately 1000 mg of grape seed proanthocyanidins, between approximately 0 mg and approximately 1000 mg of red apple quercetin, between approximately 0 mg and approximately 1000 mg of red onion quercetin, and between approximately 0 mg and approximately 400 mg of Siberian ginseng. The herbal antioxidant preferably comprises a daily dosage of between approximately 0 mg and approximately 35 mg of barberry, between approximately 0 mg and approximately 35 mg of bilberry proanthocyanidins, between approximately 0 mg and approximately 75 mg of lemon bioflavonoids, between approximately 0 mg and approximately 75 mg of lime bioflavonoids, between approximately 0 mg and approximately 75 mg orange bioflavonoids, between approximately 0 mg and approximately 500 mg of curcuma, between approximately 0 mg and approximately 1 mg of garlic bioflavonoid, between approximately 0 mg and approximately 250 mg of ginkgo biloba, between approximately 0 mg and approximately 1000 mg of ginseng, between approximately 0 mg and approximately 50 mg of gotu kola, between approximately 0 mg and approximately 500 mg of grape seed proanthocyanidins, between approximately 0 mg and approximately 500 mg of red apple quercetin, between approximately 0 mg and approximately 500 mg of red onion quercetin, and between approximately 0 mg and approximately 200 mg Siberian ginseng.
The antioxidant amino acid of the composition comprises a daily dosage of between approximately 0 mg and approximately 1500 mg of acetyl-L-camitine, between approximately 0 mg and approximately 1500 mg of L-glutamine, between approximately 0 mg and approximately 1500 mg of L-lysine, between approximately 0 mg and approximately 1500 mg of L-methionine, between approximately 0 mg and approximately 1500 mg of L-taurine, between approximately 0 mg and approximately 1500 mg of N-acetyl-L-cystine, and between approximately 0 mg and approximately 800 mg S-adenosylmethionine. The antioxidant amino acid preferably comprises a daily dosage of between approximately 0 mg and approximately 800 mg of acetyl-L-camitine, between approximately 0 mg and approximately 800 mg of L-glutamine, between approximately 0 mg and approximately 800 mg of L-lysine, between approximately 0 mg and approximately 800 mg of L-methionine, between approximately 0 mg and approximately 800 mg of L-taurine, between approximately 0 mg and approximately 800 mg of N-acetyl-L-cystine, and between approximately 0 mg and approximately 800 mg of S-adenosylmethionine.
The antioxidant vitamin of the composition comprises a daily dosage of between approximately 0 mg and approximately 50,000 IU of beta carotene, between approximately 0 mg and approximately 10,400 IU of vitamin A, between approximately 0 mg and approximately 1000 mg of vitamin B1, between approximately 0 mg and approximately 10 mg of vitamin B2, between approximately 0 mg and approximately 1000 mg of vitamin B3, between approximately 0 mg and approximately 500 mg of vitamin B5, between approximately 0 mg and approximately 500 mg of vitamin B6, between approximately 0 mg and approximately 500 mg of vitamin B6 (pyridoxal 5xe2x80x2-phosphate), between approximately 0 mg and approximately 1000 mg of vitamin B12, between approximately 0 mg and approximately 3000 mg of vitamin C, between approximately 0 mg and approximately 800 mg of vitamin E, between approximately 0 mg and approximately 1000 mcg of folic acid, between approximately 0 mg and approximately 2000 mg of L-glutathione, between approximately 0 mg and approximately 400 mg of lipoic acid between approximately 0 mg and approximately 30 mg of lutein, between approximately 0 mg and approximately 15,000 mcg of lycopene, between approximately 0 mg and approximately 600 mg of ubiquinone, and between approximately 0 mg and approximately 500 mg of zeaxanthin.
The antioxidant mineral of the composition comprises a daily dosage of between approximately 0 mg and approximately 100 mcg of boron, between approximately 0 mg and approximately 200 mcg of chromium, between approximately 0 mg and approximately 50 mg of manganese, between approximately 0 mg and approximately 1000 mg of magnesium, between approximately 0 mg and approximately 200 mcg of selenium, and between approximately 0 mg and approximately 100 mg of zinc.
The composition may additionally comprise at least one component selected from the group consisting of Bomelain, papain, and betaine. These may comprise a daily dosage of between approximately 0 mg and approximately 80 mg of Bohemian, between approximately 0 mg and approximately 50 mg of papain, and between approximately 0 mg and approximately 50 mg of beeline.
The resultant synergistic antioxidant compound may comprise at least one phosphoester and at least one herbal antioxidant, at least one phosphoester and at least one antioxidant mineral; at least one phosphoester and at least one antioxidant amino acid; at least one phosphoester and at least one antioxidant vitamin; at least one herbal antioxidant and at least one antioxidant mineral; at least one herbal antioxidant and at least one antioxidant amino acid; at least one antioxidant vitamin, at least one antioxidant mineral and at least one antioxidant amino acid; at least one antioxidant mineral and at least one antioxidant vitamin; at least one antioxidant amino acid and at least one antioxidant vitamin; at least one herbal antioxidant, at least one antioxidant mineral, and at least one antioxidant amino acid; at least one herbal antioxidant, at least one antioxidant mineral, and at least one antioxidant vitamin; and at least one antioxidant mineral, at least one antioxidant amino acid, and at least one antioxidant vitamin.
A primary object of this invention is to provide a composition for treatment of neurodegenerative disorders for administration to mammals that exhibits synergistic antioxidant and restorative effects on the nervous system.
A primary advantage of this invention is a lowered dosage requirement for components.